Arterial hypertension in systemic sclerosis.

Introduction: Arterial hypertension (AH) is common in systemic connective tissue diseases. Aim: To evaluate the incidence of AH in patients with systemic sclerosis (SSc) and to present clinical characteristics of the group diagnosed with AH. Material and methods: The study involved 108 patients with SSc divided into two groups: with AH (+) - 45 and AH (-) - 63. Moreover, the serological profile, scleroderma renal crisis, involvement of internal organs and mortality were determined. The kidney function was assessed based on creatinine concentration and the estimated glomerular filtration rate (eGFR). Results: AH was diagnosed in 47/108 SSc patients (41.7%). The age difference among patients was statistically significant and was higher in the AH (+) SSc group (p = 0.026). The incidences of oesophageal involvement (p = 0.011), digital ulcerations (p = 0.017), and mortality (p = 0.019) were found to be significantly higher in the AH (+) SSc group. Scleroderma renal crisis was observed in 9/108 patients (8.3%). The incidence of chronic kidney disease (CKD) was higher in the AH (+) SSc group, both of stage 2 (p = 0.013) and 3 (p = 0.07). Stages 4 and 5 of CKD were found only in the group with AH. Moreover, this group had a higher incidence of elevated uric acid (p = 0.007). Conclusions: AH is relatively common in patients with SSc and is associated with a significantly more severe course of the disease and higher frequency of renal involvement.

Clinical consequences of the presence of anti-RNA Pol III antibodies in systemic sclerosis.

INTRODUCTION: Anti-RNA polymerase III (a-RNA Pol III) antibodies are marker antibodies in patients with systemic sclerosis (SSc). AIM: To assess the prevalence of a-RNA Pol III in patients with SSc and to identify the differences in the disease picture in SSc patients with and without a-RNA Pol III antibodies. MATERIAL AND METHODS: The study was performed in 126 SSc patients. The subtype of SSc, incidence of internal organ involvement, malignancy, death and serological profiles were determined in the entire group. The study groups were studied according to the presence of antibodies by applying the commercial test - EUROLINE SSc Profile. Due to the presence of a-RNA Pol III, patients were divided into two groups: the a-RNA Pol III (+) SSc group of 19 patients and the a-RNA Pol III (-) SSc group of 107 patients. RESULTS: A-RNA Pol III were present in 19/126 patients with SSc (15%), 13/19 (68.4%) patients had no other SSc marker antibodies. A-RNA Pol III were more common in patients with diffuse cutaneous SSc (p = 0.049). We showed a significant positive association between a-RNA Pol III and occurrence of malignancy (p = 0.007), scleroderma renal crisis (p = 0.001) and decreased DLCO (p = 0.007). CONCLUSIONS: Anti-a-RNA Pol III antibodies are common in patients with SSc, particularly with a diffuse subtype. In more than 50% of patients with a-RNA Pol III antibodies, they may be present as the sole marker of antibodies. In SSc, a-RNA Pol III antibodies are frequently associated with malignancy occurrence, kidney and lung involvement.

[Epigenetic disturbances in systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that results in uncontrolled immune system activation and overproduction of autoantibodies. The pathogenesis of the disease is complex and not fully understood, nevertheless, genetic and environmental factors play an important role. So far, about 30 genes have been identified to be involved in the SLE pathomechanism. However, not all genetically predisposed individuals develop the disease. This phenomenon can be associated with epigenetic changes that occur under the influence of environmental factors. They can affect gene expression and are potentially hereditary, but do not lead to changes in the nucleotide sequence. Epigenetic dysfunctions, identified in the course of the disease, lead to changes in the expression of genes that play a key role in maintaining the body's immune tolerance. Major mechanisms of epigenetic variability are: DNA methylation, histone protein modification, non-coding RNA expression, as well as gene imprinting. The major epigenetic dysfunctions affecting the pathogenesis of the disease are global hypomethylation on CD4+ T cells resulting from ERK signaling pathway regulation, histone hypoacetylation, histone H3 lysine methylation, and reactivation of inactive chromosome X. In lupus patients, various epigenetic mechanisms interact with each other, enhancing the expression or silencing of genes responsible for the production of pro-inflammatory and anti-inflammatory cytokines and activation of autoreactive B-lymphocytes.

[Serum free light chains for monitoring systemic lupus erythematosus activity].

OBJECTIVE: Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease leading to chronic inflammation of numerous tissues and organs. The search for clinically useful markers of its activity is ongoing. At present, it is suggested that serum free light chains (FLC) may be useful in assessing SLE activity. The aim of study: To investigate the relationship between serum levels of free light chains (FLC) and the activity of SLE. PATIENTS AND METHODS: Material and methods: Eighty-four SLE patients (75 female; 9 men) aged 34.9±11.8 years, with the disease duration of 6.2±5.2 years, were included. The disease activity was assessed by: circulating C3 and C4 complement components levels, anti-double-stranded DNA (anti-DNA), SLEDAI-2K scale and levels of FLC. We also assessed the relationship between levels of FLC and clinical manifestations of SLE. RESULTS: Results: Median serum levels of FLC κ and FLC λ were 25.9 ± 15.6mg/L and 21.2 ± 9.4 mg/L in SLE pts, respectively. Serum levels of FLC κ were positive in 60 SLE pts (71.4%) and FLC λ in 20 SLE pts (23.8%). The significant correlations were found between levels of FLC κ, FLC λ and of anti-dsDNA (p=0.01; r=0.27); (p=0.001; r=0.35), C3 complement (p<0.02; r= -0.25); (p<0.004; r= -0.31), C4 complement (p<0.04; r= -0.22); (p<0.006; r= -0.3) and SLEDAI -2K (p<0.009; r=0.28); (p<0.001; r=0.35). The SLE pts with arthritis / myositis and hematologic symptoms had significantly higher FLC levels than those without. CONCLUSION: Conclusion: Measurement of serum levels of FLC can help in the periodical assessment of the disease activity in SLE pts.

Overlap syndromes in systemic sclerosis.

INTRODUCTION: It is known, that course of the disease differs between overlap syndromes (OS) and systemic sclerosis (SSc) group. AIM: To compare the prevalence of OS in limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous SSc (dcSSc) and to analyze the presence of different manifestations in the SSc and OS group. MATERIAL AND METHODS: The study included 126 European Caucasian SSc patients (99 females and 27 males) hospitalized consecutively in the Department of Rheumatology and Connective Tissue Diseases. Patients fulfilled the American College of Rheumatology (ACR) classification criteria of SSc (57 - dcSSc and 69 - lcSSc). The study groups were determined according to the subtype of SSc, coexistence of other connective tissue diseases (CTDs), and incidence of clinical and serological manifestations. RESULTS: In our SSc study group, 28/126 patients (22%) were affected by more than one CTD. The prevalence of OS was significantly higher in the lcSSc group - 33% (23/69) compared to the dcSSc group - 8% (5/57). We found that mortality and digital ulcers were significantly higher, whereas kidney involvement and arthritis were significantly lower in the SSc group compared to the OS group. The prevalence of anti-topoisomerase I (a-Scl-70) was significantly higher, and prevalence of anti-PM/Scl, anti-Ro-52 antibodies was significantly lower in the SSc group compared to the OS group. CONCLUSIONS: Overlap syndromes were more common in lcSSc than in dcSSc. The course of the disorder and internal organ involvement were different in OS compared to SSc patients.

Influence of antiphospholipid antibody positivity on glomerular filtration rate markers in a group of systemic sclerosis patients - a 24-month observation.

AIM OF THE STUDY: The aim of the study was the assessment of changes in the glomerular filtration rate (GFR) during long-term observation in a group of systemic sclerosis (SSc) patients with and without chronic antiphospholipid (aPL) antibody positivity. MATERIAL AND METHODS: The observation comprised 50 patients - 23 with diffuse cutaneous SSc - dcSSc and 27 limited cutaneous SSc - lcSSc. After 24 months we assessed 27 patients (9 died, 14 lost follow up); 24 patients (88%) were treated chronically with angiotensin-converting-enzyme inhibitors (ACEIs). Patients were investigated for the presence of aPL: to cardiolipin and to ß2 glycoprotein I in IgM and IgG classes. Serum levels of creatinine (S-Cr), cystatin C and creatinine clearance values were determined in all patients. According to the presence of a significant level of at least one of aPL antibodies, pts were divided into groups: group I aPL positive: 14 patients, group II aPL negative - 13 patients. RESULTS: We did not find significant differences in S-Cr, cystatin C levels and creatinine clearance before and after 24 months of observation between both groups. In follow up observations, the presence of anti-centromere antibodies was significantly more frequent in the aPL positive, as compared to the aPL negative group (p = 0.01). In follow up observations, the level of anticardiolipin antibodies in IgG class was significantly higher in dcSSc compared to lcSSc patients (p = 0.02). CONCLUSIONS: In long-term observation chronic positivity for aPL antibodies does not significantly decrease the GFR in patients with SSc treated with ACEIs.

Autoantibodies against gliadin in rheumatoid arthritis and primary Sjögren's syndrome patients.

INTRODUCTION: Patients with rheumatoid arthritis (RA) and those with primary Sjögren's syndrome (pSS), beside non-specific antibodies, present with organ-specific autoantibodies, including those typical of celiac disease (CD). In the pathogenesis of CD, a role is played by anti-tissue transglutaminase, anti-endomysium, and anti-gliadin (AGA) antibodies. CD can be comorbid with RA and pSS. The aim of the study was to evaluate the prevalence of AGA in RA and pSS patients and discussion of their clinical significance. MATERIAL AND METHODS: The study included 121 patients with RA and 30 patients with pSS. IgG AGA were determined by ELISA method. Additionally, the presence of IgG antimitochondrial antibodies (AMA) was determined in all patients. A further observation included patients with AGA. RESULTS: In the RA group, AGA were detected in five patients (4.1%), and in the pSS group - in two patients (6.7%). All patients in the pSS AGA (+) had AMA and autoimmune thyroid disease (AITD). These differences were statistically significant compared to the pSS AGA (-) and AMA (+) group (p=0.002) and the AGA (-) and AITD (+) group (p=0.003). At the time of the study, none of the patients had been diagnosed with CD. CONCLUSIONS: AGA, typical of CD, are significantly more frequently detected in patients with RA and pSS than in the general population. The presence of autoantibodies may have an impact on the clinical picture of the disease and further medical procedures. CD testing is warranted in selected patients.

Prevalence of selected organ-specific autoantibodies in rheumatoid arthritis and primary Sjögren's syndrome patients.

OBJECTIVES: The aim of the study was to investigate the prevalence of selected organ-specific autoantibodies in rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) patients, and discuss their clinical significance. MATERIAL AND METHODS: The study included 121 RA and 30 pSS patients. Sera were tested for the presence of autoantibodies to thyroid peroxidase (anti-TPO), thyroglobulin (anti-TG), TSH receptor (TRAbs), mitochondrial antigen M2 (AMA-M2-3E) and gliadin-analogous fusion peptides (anti-GAF(3X)) using the ELISA method. Non-organ-specific antibodies were determined: rheumatoid factor in IgM class, anti-citrullinated peptide antibodies and antinuclear antibodies. The occurrence of antibodies was also examined with regards to RA activity. RESULTS: The following autoantibodies were detected in RA patients: anti-TPO - 13 (10.7%), anti-TG - 6 (5%), AMA-M2-3E - 3 (2.5%), anti-GAF(3X) - 5 (4.1%). The respective levels of these autoantibodies in pSS patients were 3 (10%), 2 (6.7%), 4 (13.3%) and 2 (6.7%). Polyautoimmunity was confirmed in 34 RA patients (including 20 cases of autoimmune thyroid disease [AITD]) and in 6 pSS patients (6 cases of AITD). When RA patients were divided into anti-TPO positive and anti-TPO negative groups, we found a statistically significant relationship between groups regarding age and hemoglobin concentration. In pSS patients the anti-TPO positive group was less likely to use immunosuppressive drugs as compared with the anti-TPO negative group. Anti-TPO was significantly more frequently detected in RA + AITD vs. RA, RA + SS + AITD vs. RA and in pSS + AITD vs. pSS patients. CONCLUSIONS: Organ-specific autoantibodies are relatively frequently observed in patients with RA and pSS. Their presence is connected with the clinical picture of the diseases.

Comparison of clinical and serological parameters in female and male patients with systemic sclerosis.

OBJECTIVES: The course of systemic sclerosis (SSc) can differ in female and male patients. According to the literature the incidence rates of diffuse cutaneous SSc, scleroderma renal crisis and digital ulceration are higher in male patients. The aim of the study was to compare selected clinical and serological parameters in male and female patients with SSc. MATERIAL AND METHODS: The study encompassed 101 European Caucasian patients with SSc, including 23 men, hospitalized in the Department of Rheumatology. Patients fulfilled the American Rheumatism Association (ARA) classification criteria for SSc. The study groups of men and women were assessed according to the SSc subtype, incidence of internal organ involvement and presence of antinuclear antibodies considered SSc markers. RESULTS: Diffuse cutaneous (dc) SSc was observed more commonly in men than in women (13/23 vs. 25/78; p = 0.03). The time from the development of Raynaud's phenomenon to the diagnosis was significantly shorter in male compared to female patients (3.2 ±4.7 vs. 7.5 ±7.1; p = 0.01). The incidence of scleroderma renal crisis (SRC) was significantly higher (3/23 vs. 2/78; p = 0.04) and of other calcifications significantly lower in the male group compared to the female group (1/23 vs. 20/78; p = 0.02). CONCLUSIONS: We concluded that the incidence of dcSSc is higher in men compared to women. The time from the development of Raynaud's phenomenon to the diagnosis is shorter in the male compare to female group. The incidence of SRC is higher, whereas that of calcifications is lower in SSc men. The serological profiles of female and male patients with SSc are comparable.

Antiphospholipid antibodies during 6-month treatment with infliximab: a preliminary report.

BACKGROUND: The introduction of tumor necrosis factor (TNF) antagonists (adalimumab, infliximab, and etanercept) was a major advance and was highly important and beneficial in most rheumatoid arthritis (RA) patients. The adverse effects of this treatment are infrequent, but include opportunistic intracellular infection (especially the reactivation of latent Mycobacterium tuberculosis); exacerbation of demyelinating disorders; and the production of various types of antibodies such as antinuclear antibodies (ANA) or double-stranded DNA autoantibodies (dsDNA) and antiphospholipid antibodies (aPL) such as anti-cardiolipin antibodies (aCL) and anti-B2GP-I antibodies (B2GP-I). The aim of the study was to determine the prevalence of aCL and B2GP-I in IgM and IgG classes, using ELISA tests, during 6 months of follow-up in patients with refractory RA successfully treated with infliximab. MATERIAL/METHODS: We determined the prevalence of aCL and B2GP-I in IgM and IgG classes, using ELISA tests, during 6 months of follow-up in patients with refractory RA successfully treated with infliximab. RESULTS: We observed a statistically important increase only in the group of B2GP-I IgM (p<0.05). There are contradictory results concerning the ability of infliximab to induce aPL, but most authors confirm this phenomenon. CONCLUSIONS: Further investigations are needed to determine if the new aPL appears in patients with ß2-GPI gene polymorphisms such as leucine-to-valine substitution at position 247, which can lead to a conformational changes in ß2-GPI protein, leading to aPL synthesis. The role of aPL in pathogenesis of APS is still unclear, but we should remember the immunogenic aspect of TNF antagonist treatment. Therefore, we recommend early detection of aPL and observation of the patient, paying special attention to signs and symptoms of thromboembolism.

Serological profile of patients with systemic sclerosis.

INTRODUCTION: The systemic sclerosis-associated autoantibodies include anti-centromere, anti-topoisomerase I (anti-topo I), anti-RNA polymerase III, anti-fibrillarin, anti-Th/To, and anti-PDGFR. A specific serological profile is connected with clinical manifestations and prognosis in systemic sclerosis (SSc). OBJECTIVES: The aim of the study was to assess the serological profile in limited cutaneous and diffuse cutaneous SSc (lcSSc and dcSSc). PATIENTS AND METHODS: 87 (68 female and 19 male) consecutive SSc patients treated between 2006 and 2011 were assessed. Patients fulfilled the American College of Rheumatology classification criteria of SSc: 35 - dcSSc and 52 - lcSSc. The following marker antibodies were determined: anti-topo I, anti-centromere A and B (CENP A, CENP B), anti-RNA polymerase III (RP11, RP 155), anti-fibrillarin (U3RNP), anti- -NOR90, anti-Th/To, anti-PM-Scl-100, anti-PM-Scl-75, anti-Ku, anti-Ro-52, anti-PDGFR. The presence of antibodies was assessed using a test - EUROLINE Systemic Sclerosis Profile. RESULTS: 82 patients (94%) had positive antinuclear antibodies; anti-topo I - 29 patients; anti-CENP-A - 20 and anti-CENP-B - 20; anti-RP11 - 9 and anti-RP155 - 7; anti-U3RNP - 1; anti-NOR90 - 6; anti-Th/ To - 3; anti-PM-Scl-100 - 7; anti-PM-Scl-75 - 11; anti-Ku - 5; anti-Ro-52 - 23 patients. We found significant differences in prevalence of anti-topo I: 25/35 vs. 4/52 p=0.0000; anti-CENP A: 0/35 vs. 20/52 p=0.0001; anti-CENP B: 0/35 vs. 20/52 p=0.0001 between dcSSc and lcSSc. CONCLUSIONS: Some antibodies in SSc, e.g. anti-topo I and anti-centromere, are useful in defining the clinical subset of disease and provide prognostic information. There are no significant differences in the prevalence of other autoantibodies associated with SSc between dcSSc and lcSSc patients.

Late-age onset systemic sclerosis-clinical and serological characteristics.

The clinical course and serological profile of the late-age onset systemic sclerosis (LAO SSc) and the early-age onset SSc (EAO SSc) was compared. The study enrolled 157 patients that fulfilled the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification criteria for systemic sclerosis (SSc). Among them, 69 had diffuse cutaneous SSc (dcSSc) and 88 limited cutaneous SSc (lcSSc). Within this population, 39 patients developed the disease over the age of 60 years old (LAO SSc) and 118 prior to that age (EAO SSc). The subtype of SSc, the incidence of internal organ involvement, the prevalence of malignancy, mortality, and serological profile were compared between both groups. The LAO SSc was observed in 39 of total 157 patients with SSc and exhibited a notably higher prevalence of pulmonary arterial hypertension (p = 0.014), heart involvement (p = 0.0014), and renal involvement (p = 0.0002). The occurrence of arthralgias was less common in the LAO SSc group (p = 0.02) than in the EAO SSc group. Furthermore, in the LAO SSc group, the prevalence of anti -RNA polymerase III antibodies (p = 0.008) and antiPM/Scl antibodies (p = 0.048) were significantly lower than in the EAO SSc group. On the other hand, higher anti-Th/To antibody levels (p = 0.014) were recorded in the LAO SSc group. Approximately 25% of SSc patients experienced a delayed onset of the disease after the age of 60 years old. Some clinical and serological features of late-onset SSc were markedly different from that in early-onset disease. Particularly noteworthy is the fact that involvement of internal organs such as heart and kidneys, as well as pulmonary arterial hypertension were much more often observed among patients with LAO SSc which in our suggestion may be referred to age-related co-morbidities. Key Points • Significant differences in clinical and serological profile of the disease were found between late-age onset (LAO) and early-age onset (EAO) SSc. • Incidence of dcSSc as well as prevalence of anti-RNA polymerase III and anti-PM/Scl antibodies were found to be lower in patients over 60 years old compared to those before 60, but regardless of the age of the disease onset. • Internal organ morbidity, notably pulmonary arterial hypertension, renal impairment and heart disease were significantly more common in elder SSc patients as well as in those with late disease onset. • These findings may suggest an impact of age-related co-morbidities on the course of late-age onset SSc.

Antibodies against cyclic citrullinated peptide don't decrease after 6 months of infliximab treatment in refractory rheumatoid arthritis.

Anti-citrullinated peptide antibodies (ACPA) and the rheumatoid factor (RF) are well-established serological markers for rheumatoid arthritis (RA). ACPA are very useful in the diagnosis of RA, especially at the early stages of the disease when ACPA have a greater diagnostic value than RF. The aim of the study was to assess the influence of infliximab treatment on RF IgM and ACPA serum levels and RA activity during 6 months of treatment. Thirty-two patients with refractory RA were treated with infliximab during a 6-month period. At baseline, 3 and 6 months of treatment the patients were examined for the number swollen and tender joints out of 28 (SJC, TJC) and the visual analogue scale of arthritis activity according to the patient (VAS). Serum samples were tested for erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP), ACPA and RF IgM. The disease activity score (DAS-28) parameter was also calculated at the same time. During the course of our study, we observed statistically significant improvement in ESR, CRP, TJC, SJC, VAS DAS-28, and RF IgM after 3 and 6 months of infliximab treatment when compared to the baseline, whereas the ACPA level remained unchanged after 3 and 6 months of treatment (P = 0.96 and P = 0.85). The changes in the ACPA level are not a factor for evaluation of successful infliximab treatment but the changes in RF IgM are. According to different behavior of these antibodies during infliximab treatment, we suggest that the roles of ACPA and RF in the pathogenesis of RA are different.

The prevalence and significance of anti-PM/Scl antibodies in systemic sclerosis.

INTRODUCTION: Anti-PM/Scl (a-PM/Scl) antibodies are found in different systemic autoimmune diseases such as polymyositis, dermatomyositis, systemic sclerosis (SSc) and overlap syndromes. According to literature, they are detected in approx. 2% of SSc patients, but their presence is more common in SSc with myositis overlap. OBJECTIVE: The aim of the study was to assess the prevalence of a-PM/Scl in patients with SSc and to identify differences in the clinical profile of the disease in patients with the presence of a-PM/Scl. MATERIAL AND METHODS: The study was performed on 126 European Caucasian SSc patients (98 females and 28 males) hospitalized consecutively in the Department of Rheumatology and Connective Tissue Diseases. The study group was analyzed for the potential presence of a-PM/Scl using a commercial test - EUROLINE Systemic Sclerosis Profile. The detection and interpretation were carried out electronically using the specific Euroimmun - EUROLineScan programme. The subtype of SSc, incidence of internal organ involvement and serological profile were determined in the entire group. Due to the presence of a-PM/Scl, patients were divided into two groups: a-PM/Scl (+) SSc - 22 patients and a-PM/Scl (-) SSc - 104 patients. RESULTS: A-PM/Scl was detected in 22/126 patients with SSc (17.5%). A strong correlation was found between a-PM/Scl and myalgia or myositis (p = 0.0379), hand joints contractures (p = 0.0002) and the prevalence of overlap syndrome (p = 0.0142). There were no relationships between the presence of a-PM/Scl and subtypes of SSc, other organ involvement, digital ulcers or calcinosis. CONCLUSIONS: Anti-PM/Scl antibodies are fairly common in patients with systemic sclerosis. In SSc, anti-PM/Scl antibodies are frequently associated with myalgia or myositis, hand joint contractures and an overlap syndrome.

The value of anti-CarP and anti-PAD4 as markers of rheumatoid arthritis in ACPA/RF negative rheumatoid arthritis patients.

BACKGROUND: Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers. The purpose of this study is to evaluate the value of anti-CarP and anti-PAD4 in a well-characterized population of RA patients and healthy controls (HCs). METHODS: A total of 122 RA patients and 30 HCs were enrolled in the study. Serum levels of ACPA, anti-PAD4, anti-CarP and RF were determined by enzyme-linked immunosorbent immunoassays (ELISAs). Synthetic carbamylated peptides were used in the ELISA assay to determine the protein targets of the anti-CarP antibodies. RESULTS: Rates of ACPA, RF, anti-PAD4 and anti-CarP positivity were 85.2%, 67.2%, 55.7% and 46.7% in RA, and 0%, 0%, 6.7% and 6.7% in HC respectively. In the RA population, 25.4% of patients had all four types of antibodies positive, while 6.6% had no antibodies. There was a significant correlation between anti-PAD4 and ACPAs (r s = 0.39), RF and ACPAs, (r s = 0.3) and RF and anti-CarP, (r s = 0.3). There was no correlation between ACPAs and anti-CarP. Anti-CarP positivity was noted in 49 (47.1%) and 45 (54.9%) of ACPAs and RF positive patients respectively. In addition, five anti-CarP+ patients did not have ACPA nor RF. CONCLUSION: Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.

Adiponectin and leptin serum concentrations in patients with rheumatoid arthritis.

Adipose tissue is regarded as an active metabolic and endocrine organ producing adipokines. The purpose of the study was to evaluate adiponectin and leptin concentrations in rheumatoid arthritis (RA) patients (pts) in relation to disease duration and activity. The study group consisted of 80 RA pts. Serum adiponectin and leptin concentrations remained within normal ranges. Adiponectin concentration correlated positively both with the age and disease duration. Both adipokines levels correlated negatively with glomerular filtration rate. There were significant positive correlations between adipokines' concentrations and lipid profile components (between adiponectin and HDL-cholesterol, leptin and total cholesterol and LDL-cholesterol). In pts with long-standing RA, there was a negative correlation between adiponectin and numbers of tender, swollen joints and a positive relationship between leptin level and DAS28. The results confirm adipokines' involvement in the process of inflammation and atherosclerosis: protective and antiinflammatory adiponectin effect and proatherogenic and proinflammatory leptin function.

Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis.

Protein citrullination is carried out by peptidylarginine deiminase type 4 (PAD4) enzyme. As a consequence of this process, post-translationally modified proteins are formed that become antigens for anti-citrullinated protein antibodies (ACPA). The study aimed at identifying whether the PADI4 gene is subject to epigenetic regulation through methylation of its promoter region, whether the degree of methylation differs in healthy individuals vs. rheumatoid arthritis (RA) patients and changes in correlation with ACPA, anti-PAD4 and disease activity. A total of 125 RA patients and 30 healthy controls were enrolled. Quantitative real-time methylation-specific PCR was used to analyze the methylation status. ACPA and anti-PAD4 antibodies were determined in serum by enzyme-linked immunosorbent immunoassay. The differences were observed in the degree of PADI4 gene promoter methylation between RA patients and HC, along with an upward trend for the methylation in RA, which was inversely proportional to the disease activity. A weak or modest negative correlation between the degree of PADI4 gene methylation and anti-PAD4, disease activity score (DAS28) and ACPA level has been found. The elevated methylation is associated with lower disease activity, lower levels of ACPA and aPAD4. The methylation degree in this area is growing up during effective treatment and might play a role in the RA pathophysiology and therefore could be a future therapeutic target.

The presence of particular criteria and noncriteria antiphospholipid antibodies in patients with uterine malignancies.

INTRODUCTION: Currently, there have been limited data on the presence of antiphospholipid antibodies (aPLs) in patients with uterine malignancies (UMs). OBJECTIVES: We aimed to determine whether criteria and noncriteria aPLs are present in patients with UMs and associated with the thrombotic risk, as compared with patients with noncancerous gynecological diseases (NCGDs). PATIENTS AND METHODS: The study involved 151 women scheduled for gynecological surgery. The patients were divided into the UM group (n = 70) and the NCGD group (n = 81). The Antiphospholipid 10 Dot assay was used to detect criteria and noncriteria aPLs before surgery. The study patients were considered positive for thrombosis if they exhibited signs of thrombosis within the 2­year follow­up period after surgery. RESULTS: Positive results for aPLs were obtained in 17/70 patients with UMs (24.3%) and in 6/81 patients with NCGDs (7.4%) (P = 0.008). Particular noncriteria aPLs (antiphosphatidic acid, antiphosphatidylserine, anti-annexin V, and antiprothrombin antibodies) yet no criteria aPLs (anticardiolipin and anti-ß2­glycoprotein I antibodies) were more frequently found in patients with UMs than in those with NCGDs. Thrombosis was diagnosed in 9/70 patients (12.9%) in the UM group and in 3/81 patients (3.7%) in the NCGD group (P = 0.03). CONCLUSIONS: Antiphospholipid antibodies were present at significant levels in patients with UMs. Noncriteria aPLs yet no criteria aPLs were more frequently found in patients with UMs than in those with NCGDs. The incidence of thrombosis was significantly higher in patients with UMs.

Hypermethylation of the miR-155 gene in the whole blood and decreased plasma level of miR-155 in rheumatoid arthritis.

OBJECTIVES: miR-155 plays a critical role in the inflammatory process and in diseases such as rheumatoid arthritis (RA). miR155 gene expression is regulated by its gene promoter region CpG island methylation. Previous studies have shown inconsistent changes in circulating levels of mir-155 in RA patients. The aims of our study were to evaluate miR-155 levels in plasma, to investigate its gene methylation level, and to correlate these levels with RA disease activity. METHODS: One hundred and twenty-five patients with RA, and 30 age and sex-matched healthy controls (HC) were enrolled. Whole blood and plasma samples were collected and stored at -80°C until analysis. DAS28 score at the time of the blood draw was used to assess RA disease activity. The methylation status of miR-155 host gene was determined in whole blood by quantitative real-time methylation-specific PCR (qPCR). miR-155 expression levels were evaluated by quantitative reverse transcription PCR. RESULTS: We found significantly lower circulating miR155 levels in RA patients compared to HC. Interestingly, the miR-155 gene methylation level was significantly higher in RA patients than in HC. miR-155 levels did not correlate with ACPA or RF positivity or disease activity. CONCLUSIONS: We show here higher miR-155 methylation in whole blood and lower plasma miR155 expression in RA patients in comparison to HC. The evaluation of miR-155 host gene methylation status or miR155 plasma level might be a potentially useful marker in RA determination.

ß2-microglobulin as a marker of systemic lupus erythematosus activity.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by alternating periods of activity and remission. A portion of the patients suffers from the chronically active form of the disease. The search for clinically useful markers of its activity is ongoing. At present, it is suggested that ß2-microglobulin (ß2M) may be useful in assessing SLE activity. OBJECTIVES: The objective of the paper was to investigate the relationship between serum ß2M concentration and SLE activity. MATERIAL AND METHODS: The study group consisted of 69 SLE patients (62 women and 7 men), aged 34.5 ±11 years (19-69). Patients with kidney failure and infection were excluded from the study group. The concentration of ß2M was measured using an ELISA test. SLE activity was assessed with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and by measuring the levels of C3 and C4 complement components, anti-double stranded DNA antibodies (anti-dsDNA antibodies) and ß2M. The relationship between ß2M and the clinical manifestation of SLE was also covered in the study. RESULTS: The study revealed a statistically significant correlation between ß2M concentration and SLEDAI-2K disease activity index (p < 0.05; r = 0.6), anti-dsDNA titer (p < 0.05; r = 0.3), and C4 component serum level (p < 0.05; r = -0.3). ß2M concentration was significantly higher in patients with arthritis and/or myositis (p = 0.005), vasculitis (p = 0.005), and hematological manifestations of SLE (p = 0.02). CONCLUSIONS: Periodical determination of ß2M concentration in SLE patients may prove helpful in assessing the disease activity.